Sodium Carbonate → HCID 89996050, compound

HRID 1480809Notes

Reaction equation

HRID 1480809 reaction equation
Br[C:2]1[C:8]([CH3:9])=[CH:7][C:5]([NH2:6])=[C:4]([O:10][CH3:11])[CH:3]=1.[CH3:12][N:13]1[CH:17]=[C:16](B2OC(C)(C)C(C)(C)O2)[CH:15]=[N:14]1.C(=O)([O-])[O-].[Na+].[Na+]>CCO.C1(C)C=CC=CC=1.O.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:11][O:10][C:4]1[CH:3]=[C:2]([C:16]2[CH:15]=[N:14][N:13]([CH3:12])[CH:17]=2)[C:8]([CH3:9])=[CH:7][C:5]=1[NH2:6]

Participants

9

Reactant 3

HCID 10340Sodium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 14952458HCID 14952458, compound

Product 1

HCID 89996050HCID 89996050, compoundYield 39.8%

Reagents, catalysts & solvents 5

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 4-bromo-2-methoxy-5-methylaniline (Preparation 39, 350 mg, 1.620 mmol) in EtOH (2.5 mL), toluene (2.5 mL) and water (2.5 mL) was added 1-methylpyrazole-4-boronic acid pinacol ester (404 mg, 1.944 mmol), sodium carbonate (343 mg, 3.24 mmol) and Pd(PPh3)4 (225 mg, 0.194 mmol). The reaction mixture was heated to 80° C. for 2.5 hours, under nitrogen. The reaction mixture was cooled to room temperature and diluted with EtOAc (30 mL), washed with water (30 mL) and brine (30 mL), dried (MgSO4) and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with 0-5% MeOH in DCM to give the title compound (140 mg, 36%). 1H NMR (500 MHz, CDCl3): δ 7.56 (d, J=0.5 Hz, 1H), 7.39 (s, 1H), 6.75 (s, 1H), 6.63 (s, 1H), 3.96 (s, 3H), 3.86 (s, 3H), 3.76 (br s, 2H), 2.27 (s, 3H).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washwashed with water (30 mL) and brine (30 mL)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by silica gel column chromatography
  6. washeluting with 0-5% MeOH in DCM

Sources & evidence

ORD record
ord-e20fb02e28a144d2bdfa8f389fc9f09e
Source dataset
uspto-grants-2016_08
Patent number
US09409907B2

Reaction notes

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